Which drugs reduce dyskinesis in patients with Parkinson disease (PD)?

The FDA approved amantadine (Gocovri) extended-release (ER) capsules for the treatment of dyskinesia in Parkinson disease patients receiving levodopa-based therapy, with or without concomitant dopaminergic medications. Amantadine ER, previously known as ADS-5102, is the first drug FDA-approved for this indication.

The safety and efficacy of amantadine ER was seen in two Phase 3 controlled trials in Parkinson disease patients with dyskinesia. In the Easy LID trial, amantadine ER-treated patients had statistically significant and clinically relevant reductions in dyskinesia as per the Unified Dyskinesia Rating Scale (UDysRS) total score vs. placebo at Week 12 (37% vs. 12%). In the Easy LID 2 trial, amantadine ER-treated patients had a 46% reduction in UDysRS compared with 16% in the placebo arm. For both studies, treatment with amantadine ER increased functional time daily (ON time without troublesome dyskinesia) for patients at Week 12 (3.6 hours and 4.0 hours, respectively) vs. placebo (0.8 hour and 2.1 hours, respectively).
[59, 60]

This should be considered for patients who have clinically relevant dyskinesia and who appear likely to be able to tolerate this medication. Results from the 3-month, parallel-group, washout AMANDYSK (AMANtadine for DYSKinesia) study showed that amantadine treatment maintained its antidyskinetic effect over several years in patients with Parkinson disease and levodopa-induced dyskinesia.
[61, 62]

National Collaborating Centre for Chronic Conditions. Parkinson's disease: National clinical guideline for diagnosis and management in primary and secondary care. London, UK: Royal College of Physicians; 2006.

Parkinson disease diary. The patient or caregiver should place 1 check mark in each half-hour time slot to indicate the patient's predominant response during most of that period. The goal of therapeutic management is to minimize off time and on time with troublesome dyskinesia. Copyright Robert Hauser, 1996. Used with permission.

Sagittal section, 12 mm lateral of the midline, demonstrating the subthalamic nucleus (STN) (lavender). The STN is one of the preferred surgical targets for deep brain stimulation to treat symptoms of advanced Parkinson disease.

The deep brain stimulating lead is equipped with 4 electrode contacts, each of which may be used, alone or in combination, for therapeutic stimulation.

Axial, fast spin-echo inversion recovery magnetic resonance image at the level of the posterior commissure. The typical target for placing a thalamic stimulator is demonstrated (cross-hairs).

Implantation of the deep brain stimulation (DBS) lead.

Insertion of an electrode during deep brain stimulation for Parkinson disease.

Radiograph of the skull depicting a deep brain stimulator and leads in a patient with Parkinson disease.

Lewy bodies in the locus coeruleus from a patient with Parkinson disease.

A: Schematic initial progression of Lewy body deposits in the first stages of Parkinson disease (PD), as proposed by Braak and colleagues. B: Localization of the cluster of significant volume reduction in PD compared with health control subjects. The significant cluster located in the medulla oblongata/pons is superimposed as a red blob on the mean normalized anatomic scan of all participants. The axial and sagittal sections are centered on the peak of significance (–1; –36; –49). This image using voxel-based morphometry (VBM), which searched for regional atrophy in idiopathic PD by comparing a group of subjects with the disease and a group of healthy controls. Jubault T, Brambati SM, Degroot C, et al. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI. PLoS ONE. 2009;4(12):e8247.

Gross comparison of the appearance of the substantia nigra between a normal brain and a brain affected by Parkinson disease. Note the well-pigmented substantia nigra in the normal brain specimen on the left. In the brain of a Parkinson disease patient on the right, loss of pigmented substantia nigra due to depopulation of pigmented neurons is observed.

Lewy bodies are intracytoplasmic eosinophilic inclusions, often with halos, that are easily seen in pigmented neurons, as shown in this histologic slide. They contain polymerized alpha-synuclein; therefore, Parkinson disease is a synucleinopathy.

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Contributor Information and Disclosures

Author

Robert A Hauser, MD, MBA Professor of Neurology, Molecular Pharmacology and Physiology, Director, USF Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Byrd Institute, Clinical Chair, Signature Interdisciplinary Program in Neuroscience, University of South Florida College of Medicine

Disclosure: Received consulting fee from Cerecor for consulting; Received consulting fee from L&M Healthcare for consulting; Received consulting fee from Cleveland Clinic for consulting; Received consulting fee from Heptares for consulting; Received consulting fee from Gerrson Lehrman Group for consulting; Received consulting fee from Indus for consulting; Received consulting fee from University of Houston for consulting; Received consulting fee from AbbVie for consulting; Received consulting fee from Adama.

Coauthor(s)

Kelly E Lyons, PhD Research Professor of Neurology, Director of Research and Education, Parkinson’s Disease and Movement Disorder Center, University of Kansas Medical Center

Disclosure: Received honoraria from Novartis for speaking and teaching; Received honoraria from Teva Neuroscience for speaking and teaching; Received honoraria from St Jude Medical for board membership.

Theresa A McClain, RN, MSN, ARNP-BC Advanced Registered Nurse Practitioner and Investigator, Parkinson’s Disease and Movement Disorders Center, University of South Florida College of Medicine

Disclosure: Received consulting fee from Teva for consulting; Received consulting fee from Schering Plough for consulting; Received consulting fee from Biotie for consulting; Received consulting fee from Novartis for consulting.

Thomas L Carroll, MD Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Tufts University School of Medicine and Director, The Center for Voice and Swallowing, Tufts Medical Center